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The purpose of this study is to evaluate the efficacy and safety of azacitidine,venetoclax,and flumatinib in newly diagnosed Philadelphia chromosome-positive acute leukemia and accelerated phase or blast phase chronic myeloid leukemia patients.
This is a phase Ⅱ, open-label, single-arm, single-center study in newly diagnosed Ph-positive acute leukemia and CML-AP/BP patients. The patients will receive azacitidine, venetoclax, and flumatinib regimen in the induction treatment. The patients who respond to induction treatment will undergo consolidation treatment, and an optional allogeneic hematopoietic stem cell transplantation and post-transplantation maintenance treatment with induction therapy according to patient's wishes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Azacitidine,Venetoclax,and Flumatinib Regimen | Experimental | See Detailed Description. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Azacitidine | Drug | Azacitidine: 75mg/m2 qd, d1-d7, subcutaneous injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| CMR | Complete molecular remission (CMR) was defined as undetectable BCR/ABL transcript. | End of cycle 2 (each cycle is 28 days) |
| Measure | Description | Time Frame |
|---|---|---|
| CR/CRi, MRD-negative CR, CCyR, MMR | Complete remission (CR) was defined as < 5% bone marrow blasts in an aspirate with spicules and independent of transfusions. CR with incomplete hematologic recovery (CRi) was defined as <5% bone marrow blasts, either ANC<1×10^9/L or platelets < 100×10^9/L, transfusion independence but with persistence of cytopenia. Minimal residual disease (MRD)-negative CR was defined as a leukemic cell count below the sensitivity threshold of 1×10-4 (0.01%) bone marrow mononuclear cells (MNCs) by multiparameter flow cytometry. Complete cytogenetic response (CCyR) was defined as lack of Ph in ≥ 20 bone marrow metaphases. Major molecular response (MMR) was defined as a BCR-ABL/ABL transcript ratio of 0.1% (international scale). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Xiaowen Tang, Ph.D | The First Affiliated Hospital of Soochow University | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affiliated Hospital of Soochow University | Suzhou | Jiangsu | 215006 | China |
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| Venetoclax | Drug | Venetoclax: 100mg d1, 200mg d2, 300mg d3, 400mg d4-d14 or 21, oral (Adjusted according to the peripheral blood BCR/ABL1 results on day 14) |
|
| Flumatinib | Drug | Flumatinib: 600mg qd, d4-d21, oral |
|
| End of cycle 1 and 2 (each cycle is 28 days) |
| Number of adverse events | Adverse events are evaluated with CTCAE V5.0. | End of cycle 1 and 2 (each cycle is 28 days) |
| RFS | Relapse-free survival (RFS) was the duration from the day of CR to leukemia relapse, death, or last follow-up. | 2 years |
| OS | Overall survival (OS) was the time from enrollment to death for any reason. | 2 years |
| ID | Term |
|---|---|
| D010677 | Philadelphia Chromosome |
| D015470 | Leukemia, Myeloid, Acute |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D015456 | Leukemia, Biphenotypic, Acute |
| ID | Term |
|---|---|
| D014178 | Translocation, Genetic |
| D002869 | Chromosome Aberrations |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
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| ID | Term |
|---|---|
| D001374 | Azacitidine |
| C579720 | venetoclax |
| C553360 | flumatinib |
| ID | Term |
|---|---|
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
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